Promising opportunities to improve polio vaccines

Polioviruses belong to Enterovirus C species and cause severe lesions of the nervous system. In the post-polio eradication era, the World Health Organisation recommends inactivated polio vaccines for effective long-term protection of the population. In order to meet the needs of global health, it is planned to increase the use of traditional and optimised inactivated polio vaccines and introduce new types of vaccines that are being developed based on the current understanding of RNA-containing viruses. The aim of the study was to analyse ways of improving vaccine preparations and to review promising areas for polio immunoprophylaxis development. The authors considered innovations across all stages of the technological process, aimed at obtaining optimised vaccines, as well as vaccine delivery systems. The article presents information on new vaccine strains and cell lines for vaccine production. The authors summarised the results of clinical studies of inactivated vaccines, new vaccines based on genetically stable vaccine strains of poliovirus, and vaccines containing virus-like particles. The most likely candidates for introduction are the vaccines based on virus-like particles obtained from genetically modified strains of poliovirus. At the moment, many issues related to current trends in improving the immunoprophylaxis of poliomyelitis are debatable and need to be addressed in the near future

Thiouronium Salt Derivatives Based on Vicinal Diamines as Potential Neuroprotectors

Most of the medicinal products that are currently approved and used in clinical practice for neurodegenerative diseases, in particular Alzheimer’s disease, have a compensatory mechanism of action that enhances neurotransmitter signalling. It is an urgent need to develop new medicinal products combining cognitive-enhancing, neuroprotective, and disease-specific effects resulting from a multi-target mechanism of action including, in particular, prevention of glutamate-induced neuronal calcium uptake and stabilisation of microtubules.The aim of this study was to search for potentially neuroprotective and tauopathy-alleviating medicines amongst new thiouronium salt derivatives based on vicinal diamines.Materials and methods. The study investigated the ability of thiouronium salts to block glutamate-induced 45Ca2+ uptake by synaptosomes prepared from the brain of Wistar rats. The authors evaluated effects of these new compounds on polymerisation of a preparation of C57bl mouse brain tubulin and microtubule-associated proteins. The evaluation was carried out in the presence of guanosine triphosphate (GTP) and based on specific absorbance changes at 355 nm due to formation of microtubules. The authors analysed the structure of these microtubules, using negative staining followed by transmission electron microscopy. The IC50 determination and the statistical analysis were performed using standard software (Excel and PRISM 6.02).Results. The authors developed a screening algorithm for a number of new thiouronium salt derivatives based on vicinal diamines and studied biological activity of these derivatives by the effects on glutamate-induced calcium uptake by synaptosomes and on microtubule assembly processes. The authors identified compounds suppressing glutamate-induced calcium uptake by synaptosomes, i.e. compounds with neuroprotective potential. In addition, a number of new compounds were able to stimulate GTP-dependent microtubule assembly processes. The authors observed formation of microtubules with a normal structure in the presence of isopropyl-N’-[2-(benzoylamino)-1,2-diphenylethyl]-N-ethylimidothiocarbamate hydrobromide and considered the compound a promising scaffold for further optimisation.Conclusions. Chemical modification of thiouronium salts is a promising direction for developing effective neuroprotectors and microtubule stabilisers

Перспективные направления в совершенствовании вакцин для профилактики полиомиелита

Polioviruses belong to Enterovirus C species and cause severe lesions of the nervous system. In the post-polio eradication era, the World Health Organisation recommends inactivated polio vaccines for effective long-term protection of the population. In order to meet the needs of global health, it is planned to increase the use of traditional and optimised inactivated polio vaccines and introduce new types of vaccines that are being developed based on the current understanding of RNA-containing viruses. The aim of the study was to analyse ways of improving vaccine preparations and to review promising areas for polio immunoprophylaxis development. The authors considered innovations across all stages of the technological process, aimed at obtaining optimised vaccines, as well as vaccine delivery systems. The article presents information on new vaccine strains and cell lines for vaccine production. The authors summarised the results of clinical studies of inactivated vaccines, new vaccines based on genetically stable vaccine strains of poliovirus, and vaccines containing virus-like particles. The most likely candidates for introduction are the vaccines based on virus-like particles obtained from genetically modified strains of poliovirus. At the moment, many issues related to current trends in improving the immunoprophylaxis of poliomyelitis are debatable and need to be addressed in the near future.Полиовирусы, принадлежащие к энтеровирусам группы С, являются причиной тяжелых поражений нервной системы. В эпоху после ликвидации полиомиелита Всемирная организация здравоохранения рекомендует для длительной эффективной защиты населения инактивированные вакцины против полиомиелита. Для обеспечения потребностей глобального здравоохранения предполагается увеличить применение традиционных и оптимизированных инактивированных вакцин против полиомиелита, а также внедрить вакцины нового типа, которые разрабатываются на основе современных представлений о РНК-содержащих вирусах. Цель работы — анализ аспектов усовершенствования вакцинных препаратов и обзор перспективных направлений развития иммунопрофилактики полиомиелита. Рассмотрены инновационные разработки на всех этапах технологического процесса, выполненные с целью получения оптимизированных вакцин, а также системы доставки вакцин. Представлена информация о новых вакцинных штаммах и клеточных линиях для производства вакцины. Обобщены результаты клинических исследований инактивированных вакцин, новых вакцин на основе генетически стабильных вакцинных штаммов вируса полиомиелита и вакцин, содержащих вирусоподобные частицы. Наиболее вероятно внедрение вакцин на основе вирусоподобных частиц генетически модифицированных штаммов вируса полиомиелита. В настоящее время многие вопросы, касающиеся актуальных направлений совершенствования иммунопрофилактики полиомиелита, являются дискуссионными и требуют решения в ближайшем будущем

Anthrax in the East Kazakhstan Region

Almost every year in Kazakhstan, cases of diseases of animals and people with anthrax are recorded. The incidence rate of people with anthrax in the period from 2000 to 2018 ranged from 0.01 to 0.24 per 100 thousand people. In the territory of the East Kazakhstan region, the incidence rate is higher than in the republic.Objective: a retrospective analysis of anthrax outbreaks in the East Kazakhstan region from 2000 to 2018.Methods: a retrospective analysis using statistical, cadastral data, archival funds, the results of participation in the investigation of outbreaks of infection.Results. Since 1938, cases of animal and human disease of anthrax have been recorded in East Kazakhstan. Infection of humans occurs during the slaughter of animals. In Zharma, Urjar, and Ayagozskiy areas most of all are anthrax foci of soil. In 67 % of cases, outbreaks of anthrax were recorded in these areas.Conclusion. The relative incidence rate of anthrax in people in East Kazakhstan is from 0.07 to 0.27, since 2001 it is higher than the republican indicator.In the East Kazakhstan region from 1997 to 2018, 37 people fell ill with anthrax. The form of the disease is skin, in 8.1 % secondary sepsis. In the remaining patients, the diseases were mild (70.3 %), ended in recovery. The source of human infection is mainly cattle. The isolated strains of B. anthracis have typical properties, they are included in cluster A1a, A3b (MLVA-8). The strains isolated in 2016 are similar to the strains isolated in the Almaty region (MLVA-25). Grouped with a number of European, Asian and African strains from France, Germany, Italy, Tajikistan, Pakistan, Korea and Namibia. The presence of a significant number of soil foci of anthrax in the territory of the East Kazakhstan region, not fully the implementation of veterinary and sanitary preventive measures leads to an exacerbation of the situation for anthrax

Studies of Anti-Viral Activity of Chemically Synthesized Compounds against Orthopoxviruses <I>in vitro</I>

for ST-246 and NIOC-14 is within the range of 0,001-0,004 µg/ml, and IS for both of them is > 100000. In addition, ST-246 and NIOC-14 chemical compound efficacy, concentrated up to 0,0125; 0,025 and 0,05 µg/ml, in accordance with prophylactic charts describing an impact on ectromelia virus (EV) infectivity in vitro, is consequently 0,6; 3 and 1 lg higher than in case of compound application after an hour of Vero cells infection with EV

Approaches to Reduce Adverse Effect of Vaccinia Virus in Orally Immunized Mice

Objective of the investigation was to model the adverse action of vaccinia virus (VV), caused by oral immunization of mice and to evaluate efficacy of its reduction, using therapeutic and prophylactic drugs. Materials and methods. Virological and immunological research methods were used. Results and conclusions. Reproduced was pathological action of VV in the orally infected mice. The ability to reduce the side effect and protect mice from lethal infection was demonstrated by such preparations as Metisazon, Likopid, and NIOCH-14 orally administered in the investigated schemes. Moreover preliminary single oral immunization with TEOVak smallpox vaccine before oral infection with Neurovaccine-92 strain of VV also lowered pathogenic effect and protected mice against death. All the investigated schemes of drug administration did not affect the immune response if used alongside with TEOVak smallpox vaccine and can be deployed to develop safe schemes of primary oral vaccination against smallpox. In addition, such drugs as Ribomunil, Immudon, Ingavirin can be used as means to enhance the immune response to smallpox vaccines

Results from a combined test of an electromagnetic liquid argon calorimeter with a hadronic scintillating-tile calorimeter

The first combined test of an electromagnetic liquid argon accordion calorimeter and a hadronic scintillating-tile calorimeter was carried out at the CERN SPS. These devices are prototypes of the barrel calorimeter of the future ATLAS experiment at the LHC. The energy resolution of pions in the energy range from 20 to 300~GeV at an incident angle $\theta$ of about 11$^\circ$ is well-described by the expression \sigma/E = ((46.5 \pm 6.0)\%/\sqrt{E} +(1.2 \pm 0.3)\%) \oplus (3.2 \pm 0.4)~\mbox{GeV}/E. Shower profiles, shower leakage, and the angular resolution of hadronic showers were also studied

Measurement of pion and proton response and longitudinal shower profiles up to 20 nuclear interaction lengths with the ATLAS Tile calorimeter

The response of pions and protons in the energy range of 20 to 180 GeV produced at CERN's SPS H8 test beam line in the ATLAS iron-scintillator Tile hadron calorimeter has been measured. The test-beam configuration allowed to measure the longitudinal shower development for pions and protons up to 20 nuclear interaction lengths. It is found that pions penetrate deeper in the calorimeter than protons. However, protons induce showers that are wider laterally to the direction of the impinging particle. Including the measured total energy response, the pion to proton energy ratio and the resolution, all observations are consistent with a higher electromagnetic energy fraction in pion induced showers. The data are compared with GEANT4 simulations using several hadronic physics lists. The measured longitudinal shower profiles are described by an analytical shower parameterization within an accuracy of 5-10%. The amount of energy leaking out behind the calorimeter is determined and parameterised as a function of the beam energy and the calorimeter depth. This allows for a leakage correction of test-beam results in the standard projective geometry

The Production and Qualification of Scintillator Tiles for the ATLAS Hadronic Calorimeter

The production of the scintillator tiles for the ATLAS Tile Calorimeter is presented. In addition to the manufacture and production, the properties of the tiles will be presented including light yield, uniformity and stability